Brain tumor initiating cell response to microglia
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE52127 | GEO | 2013/11/06
SECONDARY ACCESSION(S): PRJNA226782
REPOSITORIES: GEO
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Project description:Determination of the mechanism by which microglia regulate growth of brain tumor initiating cells (BTICs) and differentiation. Results identify the factors involved in the regulation and provide mechanistic basis. We subjected brain tumor initiating cells to microarray to determine the genes involved in BTICs growth and differentiation when exposed to microglia conditioned medium (MCM) for 6h. BTICs were grown in MCM or control medium for 6h, and media was removed and then the cells were subjected for RNA extraction and hybridization on Affymatrix microarrays. Three (3) control and four (4) MCM samples were generated. The overall objective was to collect the RNA from the MCM exposed differentiated BTICs.
2013-11-06 | E-GEOD-52127 | biostudies-arrayexpress
Project description:We have determined that demeclocycline reduces the growth of brain tumor initiating cells (BTICs). Specifically, we sought to obtain insights into the mechanisms by which demeclocycline directly regulates BTIC growth. Analysis of the array data identified several genes that were altered with demeclocycline treatment that could regulate BTIC growth. The study provides the mechanistic basis for the regulation of BTIC growth with demeclocycline treatment. We subjected 3 BTIC lines to microarray analyses to identify genes involved in the regulation of BTIC growth by demeclocycline. Three BTIC lines (BT012, BT025 and BT048) were treated with 10 µM demeclocycline for 6h. One (1) control and 1 treatment (demeclocycline treated) sample was generated from each BTIC line. Thus, a total of 6 RNA samples from 3 BTIC lines were obtained for microarray analysis.
2016-05-18 | E-GEOD-81515 | biostudies-arrayexpress
Project description:We have determined that demeclocycline reduces the growth of brain tumor initiating cells (BTICs). Specifically, we sought to obtain insights into the mechanisms by which demeclocycline directly regulates BTIC growth. Analysis of the array data identified several genes that were altered with demeclocycline treatment that could regulate BTIC growth. The study provides the mechanistic basis for the regulation of BTIC growth with demeclocycline treatment.
2016-05-18 | GSE81515 | GEO
Project description:We have determined that tenascin C (TNC) regulates the growth of human brain tumor initiating cells (BTICs). We have identified novel mechanisms by which TNC regulates BTIC growth. Analysis of the array data identified a number of genes that were altered with TNC treatment that could potentially regulate BTIC growth. The study provides the mechanistic basis for the regulation of BTIC growth with TNC.
2017-02-08 | GSE94640 | GEO
Project description:Glioblastomas coopt stem cell regulatory pathways to maintain brain tumor initiating cells (BTICs), also known as cancer stem cells. Notch signaling has been a molecular target in BTICs, but Notch antagonists have demonstrated limited efficacy in clinical trials. RBPJ is considered a central transcriptional mediator of Notch activity. Here, we report that pharmacologic Notch inhibitors were less effective than targeting RBPJ in suppressing tumor growth. While Notch inhibitors decreased canonical Notch gene expression, RBPJ regulated a distinct profile of genes critical to BTIC stemness and cell cycle progression. RBPJ was preferentially expressed by BTICs and required for BTIC self-renewal and tumor growth. MYC, a key BTIC regulator, bound the RBPJ promoter and treatment with a BET family bromodomain inhibitor decreased MYC and RBPJ expression. Proteomic studies demonstrated that RBPJ binds CDK9, a component of P-TEFb (positive transcription elongation factor), to target gene promoters, enhancing transcriptional elongation. Collectively, RBPJ links MYC and transcriptional control through CDK9, providing potential nodes of fragility for therapeutic intervention, potentially distinct from Notch.
2016-05-01 | GSE79735 | GEO
Project description:Transcriptome analysis on ING5-knockdown brain tumor stem cell lines Stem cell-like brain tumor initiating cells (BTICs) cause recurrence of glioblastomas, with BTIC "stemness" affected by epigenetic mechanisms. The ING family of epigenetic regulators (ING1-5) function by targeting histone acetyltransferase (HAT) or histone deacetylase (HDAC) complexes to the H3K4me3 mark to alter histone acetylation and subsequently, gene expression. Here we find that ectopic expression of ING5, the targeting subunit of HBO1, MOZ and MORF HAT complexes increases expression of the Oct4, Olig2 and Nestin stem cell markers, promotes self-renewal, prevents lineage differentiation and increases stem cell pools in BTIC populations. This activity requires the plant homeodomain region of ING5 that interacts specifically with the H3K4me3 mark. ING5 also enhances PI3K/AKT and MEK/ERK activity to sustain self-renewal of BTICs over serial passage of stem cell-like spheres. ING5 exerts these effects by activating transcription of calcium channel and follicle stimulating hormone (FSH) pathway genes. In silico analyses of The Cancer Genome Atlas (TCGA) data suggest that ING5 is a positive regulator of BTIC stemness, whose expression negatively correlates with patient prognosis, especially in the Proneural and Classical subtypes, and in tumors with low SOX2 expression. These data suggest that altering histone acetylation status and signaling pathways induced by ING5 may provide useful clinical strategies to target tumor resistance and recurrence in glioblastoma.
2017-06-24 | GSE100398 | GEO
Project description:Brain tumor initiating cells (BTICs), also known as cancer stem cells, hijack high-affinity glucose uptake normally active in brain to maintain energy demands in dynamic tumor microenvironments. Using unbiased metabolomics and genomic analyses, we discovered that de novo purine synthesis is functionally upregulated in BTICs, mediating glucose-sustained anabolic metabolism. Inhibiting purine synthesis abrogated BTIC growth, self-renewal, and in vivo tumor formation by depleting intracellular pools of purine nucleotides, supporting purine synthesis as potential therapeutic point of fragility. In contrast, differentiated brain tumor cells retained proliferative potential with targeting of purine biosynthetic enzymes, suggesting a selective dependence in BTICs. Upstream transcriptional activation of purine synthesis is mediated by MYC. Elevated expression of purine synthetic enzymes correlates with poor prognosis in glioblastoma patients. Collectively, our results suggest that a stem-like state in brain cancer is associated with metabolic reprogramming to fuel tumor hierarchy, revealing potential BTIC cancer dependencies amenable to targeted therapy.
2017-03-20 | GSE95216 | GEO
Project description:Dilsulfiram together with Copper shows efficacy against patient derived Brain Tumor Initiating Cells (BTICs) in vitro and sensitizes BTICs to the DNA damaging agent TMZ. In addition, preclinical assessment found that DSF/Cu potentiaties the efficicacy of TMZ in vivo and prolongs survival. We used microarrays to detail the global profile of gene expression underlying DSF/Cu treatment in vitro and in vivo in BTICs.
2016-03-21 | GSE76146 | GEO
Project description:we found that a proportion of human and murine brain tumor-initiating cells (BTICs) expressed programmed cell death protein (PD-1) in situ and in culture. PD-1 signaling through NF B promotes BTIC proliferation.
2020-10-30 | GSE160417 | GEO
Project description:Glioblastoma Multiforme (GBM) is the most deadly brain tumor, and currently lacks effective treatment options. Brain tumor initiating cells (BTICs) and orthotopic xenografts are widely used in investigating GBM biology and new therapies for this aggressive disease. However, the genomic characteristics and molecular resemblance of these models to GBM tumors remain undetermined. We used massively parallel sequencing technology to decode the genomes and transcriptomes of BTICs and xenografts and their matched tumors in order to delineate the potential impacts of the distinct growth environments. Using data generated from whole‐genome sequencing of 201 samples and RNA sequencing of 118 samples, we showed that typical GBM genomic driver alterations found in the tumors were retained in BTICs and xenografts. In contrast, gene expression and methylation profiles indicated higher levels of divergence, likely due to the different growth environment for each sample type. These findings suggest that a comprehensive genomic understanding of in vitro and in vivo GBM model systems is crucial for interpreting data from drug‐screens, and can help control for biases introduced by cell culture conditions and the microenvironment in mouse models.
2019-03-22 | GSE128654 | GEO